Mitochondrial CPT1-mediated fatty acid beta-oxidation (FAO) critically contributes to the accelerated metastatic expansion of triple negative breast cancer (TNBC). Hence, inhibition of FAO through active CPT1 targeting could be a promising therapeutic approach in anti-TNBC therapies. Herein, we strategically synthesized a pyrene chain end labelled copolymer bearing biotin pendants, CP4, that actively targets CPT1 and efficiently blocks FAO in metastatic TNBC. Following the comprehensive characterization and synthesis of CP4, in silico negative docking score and Ramachandran plot analyses confirmed its on-target binding potential to CPT1. As a result, CP4 disrupts mitochondrial membrane potential, generates excessive ROS, and restricts excessive ATP production by impairing mitochondrial respiration, glycolytic function, and FAO. Subsequently, CP4 suppressed FA uptake and regulated FAO-associated gene expressions, exhibiting successive metastatic growth inhibition and apoptosis induction. Also, in an animal model, CP4 demonstrated active binding to CPT1, as evidenced by the significant depletion of CPT1A expression in tumor and liver tissue, akin to the specific CPT1-targeted drug. This active targeting of CPT1 has further consolidated the healing of altered lipid and oxidative stress, resulting in remarkable tumor regression, highlighting CP4 as a promising anticancer therapy focused on mitochondrial FAO, advancing future breast cancer treatments.

Menopause is the end of the menstrual cycle in a woman’s life. At menopause, a series of physiological changes occur in women’s bodies and hormonal changes are the main cause of these changes. Several metabolic changes occur in the body at that particular period, and the constellation of these changes is referred to as metabolic syndrome. Postmenopausal women have higher chances of developing these metabolic syndromes such as cardiovascular diseases (CVDs), hypertension, diabetes, and changes in the lipid profile mostly due to changes in the level of estrogen. Thus, having an overview of common metabolic disorders, their detection, and their management can improve the overall quality of life and decrease the mortality rate in the postmenopausal group. This review has discussed the commonly occurring metabolic disorders at menopause and how these disorders can be managed and treated.

Background: Stress is a known causative factor in modulating cognitive health, which overall well-being and quality of life are dependent on. Long-term stress has been shown to disrupt the balance of the hypothalamic–pituitary–adrenal (HPA) axis. Adaptogens, such as Withania somnifera (ashwagandha), are commonly used in Ayurvedic medicine for stress relief and ameliorating HPA-axis dysfunction. The aim of this study was to support the role of a root and leaf water-extracted ashwagandha extract (WS) in stress reduction by confirming the lowest clinically validated dose for stress management (125 mg/day) in a dose-dependent clinical study in adults with self-reported high stress. Methods: An 8-week, randomized, double-blinded, placebo-controlled study to compare the effects of three different WS extract doses (125, 250 and 500 mg) was performed. A total of 131 adults were enrolled, and 98 were included in the final analysis. Attenuation of chronic stress was measured using the 14-item Perceived Stress Scale (PSS) and biochemical-related stress parameters. Results: We have shown that aqueous WS extract (roots and leaves) safely reduces mild to moderate chronic stress at doses of 125 mg, 250 mg, and 500 mg/day for 8 weeks. Conclusions: Our findings demonstrate the stress-reduction capabilities of this well-characterized aqueous extract of WS (root and leaf) at the low dose of 125 mg/day, in a dose-dependent manner, via the modulation of the HPA axis. Trial registration: This study was registered with the Clinical Trials Registry—India (CTRI) with the registration number: CTRI/2019/11/022100.

Background: More than 80% of the world's population uses herbal remedies in some form. Heavy metal contamination and the attendant health risks of Indian herbal medicines are not adequately documented. Objective: This study aimed to investigate the health risks associated with four common heavy metal contaminants, namely lead, arsenic, cadmium, and mercury, present in raw medicinal herbs cultivated or growing wild in the West Bengal state of India. Methods: A total of 197 raw herbs obtained from herbal medicine practitioners or wild plant col-lectors from 16 districts spread across 3 geographical zones (south, central, north) of West Bengal were analyzed. In accordance with AOAC specifications, all samples were dried in a hot air oven, ground into a coarse powder, and then processed and analyzed for heavy metals through atomic absorption spectrometry. The mean concentrations were estimated along with standard devia-tions, overall, zone-wise, and according to the botanical part tested. The standardized human health risk indices were calculated from the results. Results: Significant amounts of heavy metals were found in the herb samples analyzed in the order: lead in 150 samples (76.1%), arsenic in 84 (42.6%), cadmium in 77 (39%), and mercury in 47 (23.8%). Central zone samples had the highest concentrations of lead (10.06 μg/g), arsenic (0.62 μg/g), and cadmium (0.54 μg/g), while the greatest amount of mercury (0.08 μg/g) was obtained in herbs from South zone. There were also considerable variations with respect to the source of the botanical part. Lead and cadmium concentrations showed a significant positive cor-relation (r = 0.588). Although risk assessment using standardized measures indicated some risk, the human Hazard Index (HI) was less than 1 for all metals, indicating that it was mostly safe to use the herbs in the short-term. However, the risk of health issues from prolonged use still re-mains. Conclusion: Significant contaminations were identified, but exposure would mostly be within acceptable risk levels at present. However, since risk would be cumulative over time, programs need to be in place to monitor pharmaceutical herb safety, identify local sources of pollution, and take appropriate remedial action.

Honey has several nutritional and therapeutic uses due to the presence of different bioactive compounds.These substances are derived from floral nectar. Therefore, it becomes essential to identify the distinct chemical profiles of honey samples. The aim of this research was to provide an accurate, straightforward, and sensitive HPTLC approach for different types of honey verification. Eight mono floral honeys (mustard, eucalyptus, litchi, orange, tea, Indian plum, black plum and pineapple) were collected from different origin of West Bengal (eastern India) and examined. Standard procedures were followed to check the quality of each honey.The flora was identified by microscopically examining the pollen found in honeys. High-performance thin layer chromatography (HPTLC) was used to analyze lipophilic fractions of each honey. Chromatographic results identified distinct patterns of bands with specific Rf values for each type of mono floral honey. HPTLC is a simple and effective method for routine analysis and verification. It can serve as authentication for different types of honey.

A non-pathogenic strain of Ochrobactrum pseudintermedium C1 produces potent surface-active exopolysaccharides which exhibits a porous scaffold-like architecture. Such a property is quite prospective in facilitating housing of cells for in vivo tissue regeneration. This surfactant exopolysaccharide has been fabricated for augmenting such regenerative properties. Different vital parameters of the fabricated EPS like surface morphology, swelling behavior, in vitro degradation study, cytotoxicity and biocompatibility have been evaluated which helped postulate the applicative profile of this natural scaffold. Further, Ochrobactrum-borne fabricated EPS, when applied as a scaffold in monosodium iodoacetate induced experimental osteoarthritis in Wistar rat model, helped significant chondrogenesis without leaving any residual amount of scaffold. The functional restoration of knee joints, assessment of chondroitin sulfate in damaged cartilage, diminution of stress induced indicators like reactive oxygen metabolite and histopathological findings quite appreciably favored the objectives. Moreover, a single high dose exhibited considerable efficacy compared to repetitive targeted administration of the scaffold at regular intervals. Thus, this novel biological macromolecule offers a green and cost-effective alternative to various commercially available synthetic scaffolds that promote tissue regeneration.

Biochemical anomalies impairing the body’s normal metabolism are referred to as inborn errors of metabolism (IEM). Early diagnosis and management can avert the otherwise harmful situation that may occur due to inborn errors. Generally, their incidence can vary from one case in every 800 to 2500 cases. Thus, understanding the genetic defects behind the clinical presentation of the disease and their early management and treatment is the need of the hour. This review article gives an overall knowledge of the types of IEM, its pathophysiology, clinical presentation, diagnosis, and management of the disease.

The COVID-19 patients experienced acute respiratory distress during their SARS-CoV-2 infections. The present observational study was undertaken to find out the possible association between vitamin D and COVID-19 clinical severity in a tertiary care hospital from November 2021 to February 2022. Patients admitted to the hospital's Critical Care Unit (CCU) with SARS-CoV-2 illness were selected for blood vitamin D estimations. Patients' conditions were evaluated clinically and correlated with serum vitamin D levels. Out of a total of 97 COVID-19 patients selected, 64.9% were male. Clinically, 41.3% of patients had a severe COVID-19 infection, compared to a moderate infection incidence of 58.7%. Among them, 19.6% and 42.2% were found to be vitamin D deficient and vitamin D insufficient, respectively. Serum vitamin D was significantly (p<0.001) reduced with age (& LE; 60 yrs vs. & GE; 60 yrs) and with disease severe (moderate vs. severe). The insufficiency/deficiency of vitamin D was higher among the aged acute respiratory-infected COVID-19 patients. Therefore, vitamin D deficiency may be one of the main causes of severe illness in SARS-CoV-2 patients.

Background and aims: There is limited information on the chemical nature of the edible fruits of the mangrove Sonneratia apetala, which is utilized in traditional medicine in coastal areas. The goal of the current research was to identify the biologically active substances behind their therapeutic effects, particularly blood sugar regulation. Methods: To determine the chemical fingerprint of S. apetala fruit extract, reversed phase high performance liquid chromatography (RP-HPLC) and gas chromatography–mass spectrometry (GC-MS) profiling were used. The antioxidant properties were thoroughly examined. α-Amylase and α-glucosidase enzymes were also used to evaluate the impact of S. apetala fruit extract on the regulatory mechanism for the metabolism of carbohydrates. Results: S. apetala fruit extract showed high concentrations of phenolics, flavonoids, and water-soluble vitamins (C, B2, B5, and B6). Quercetin, catechin, rutin, myricetin, p-coumaric acid, ferulic acid, gallic acid, sinapic acid, and ascorbic acid were among the recognized therapeutically active substances found in RP-HPLC. The presence of β-amyrin and lupeol in S. apetala fruit extract was determined by the GC-MS profile. The carbohydrate-slitting enzymes α-amylase and α-glucosidase were also strongly inhibited by S. apetala fruit extract. Conclusion: The fruit of S. apetala contains therapeutically useful polyphenolics, triterpenoids, phytosterols, and vitamins. It can lower blood sugar absorption by blocking enzymes that break down carbohydrates and has potent antioxidant qualities.

Misfolded peptide amyloid beta (Aβ42), neurofibrillary tangles of hyper-phosphorylated tau, oxidative damage to the brain, and neuroinflammation are distinguished determinants of Alzheimer’s disease (AD) responsible for disease progression. This multifaceted neurodegenerative disease is challenging to cure under a single treatment regime until the key disease determinants are traced for their sequential occurrence in disease progression. In an early report, a novel side-chain tripeptide containing PEGylated block copolymer has been tested thoroughly in vitro and in silico for the early inhibition of Aβ42 aggregation as well as degradation of preformed Aβ42 fibril deposits. The present study demonstrates a preclinical assessment of the PEGylated block copolymer in colchicine-induced AD-mimicking rodent model. The colchicine-induced Wistar rats receiving an intranasal delivery of the block copolymer at a daily dosage of 100 µg/kg and 200 µg/kg body weights, respectively, for 14 days manifested a notable attenuation of behavioral deficit pattern, oxidative stress, and neurotransmitters’ deficiency as compared to the untreated ones. The current study also reports the ameliorative property of the PEGylated compound for progressive neuroinflammation and decreased mitochondrial bioenergetics in astrocytoma cell line, viz., U87. A closer look into the drug mechanism of action of a compact 3D PEGylated block copolymer confirmed its disintegrative interaction with Aβ42 fibril via in silico simulation. The results obtained from this study signify the potential of the novel PEGylated block copolymer to ameliorate the cognitive decline and progressive oxidative insults in AD and may envision a successful clinical phase trial. The amelioration of disease condition of colchicine-induced AD rat. Initially the rat has given colchicine via stereotaxic surgery which led to a mimicking condition of AD including neuronal death in hippocampal CA1 region. After recovery from the surgery, the rat was treated with the PEGylated block copolymer through intranasal delivery, and this has led to the decrease in neuronal death in hippocampal CA1 region. The mechanism of drug action has shown by the separation of monomer chains of Aβ42.

Objectives: The anticancer effect of an Indian herbal preparation was studied under a cancer cell line, as well as the in silico computational methods that explain the probability of protein ligands binding to ER- α and HER-2 receptors. Method: The in vitro anticancer activity of Body Revival® suspension (BR) was determined using cytotoxicity tests, cell invasion and migration assays, and metastatic protein expression assays using MCF-7 breast cancer cells. The computational predictive biological method was applied to find out the pharmacodynamic and pharmacokinetic interactions between the active molecules present in the BR and ER- α/and HER-2 of breast cancer. Results: BR showed significant and dose dependent cytotoxic effects on MCF-7 cells. The 50% effective cytotoxic dose of BR was 34.27µl/ml. It restricted invasion (26%) and migration (28%) of cancer cells than BSA control. MMP-9 and IL-6 concentration were reduced significantly (p<0.001) after treatment. Cucurbitacin B had maximum in silico binding energy score (-7.8) with ER-α, while symconoside B had with HER-2 (-8.4); but, among the other interactions between the two ligands and receptors, withaferin A had the highest affinity (-15.3). Additionally, withaferin A, symconoside A, and symconoside B curcurbitacin A demonstrated bioavailability and fulfilled safety standards. Conclusion: Body Revival® showed as a powerful multi-target inhibitor of ER- α and HER-2 that has prospective anticancer action without side effects, and may be useful in the therapy management following a successful trial in breast cancer patients. Keywords: Breast cancer, Cytotoxicity, MCF-7, ER- α, HER-2, Herbs, In Silico

Background: COVID-19 has so far affected millions of people in India. The present study was undertaken to find out the performance and reliability of rapid antigen test (RAT) in compared to reverse transcription polymerase chain reaction (RT-PCR).Methods: The pre and existing medical conditions and clinical signs and symptoms were noted. The nasopharyngeal swab samples were taken for RAT, while both nasopharyngeal and oropharyngeal swab samples were mixed in a sterile viral transported medium (VTM) for RT-PCR. All patients were examined by RAT, while symptomatic negative in RAT were re-examined by RT-PCR.Results: Total 18,965 samples were examined by RAT and 3,998 samples by RT-PCR. Among them, only 5,753 patients (30.3%) were symptomatic and 1,757 patients (9.2%) were symptomatic positive. RAT showed overall 15.2% positive cases. Only 3.7% samples exhibited false negative results in RAT, which were found positive in RT-PCR. Interestingly, Ct (cycle threshold) values were >30 in all these samples.Conclusion: Hence, specific antigen-based rapid diagnostic test (RDT) will be most useful and reliable among any other qualitative tests for screening purpose.

Body Revival is a composite traditional herbal medicine with multiple phytoconstituents recognized as anticancer therapeutic potentials.These bioactive anticancer phytoconstituents are β-asarone, cucurbitacin B, 1-hydroxytectoquinone, marmelin, methylglyoxal, mollugin, quercetin, withanone, withanolid, withaferin A etc.This review is based on mechanistic analysis of individual phytoconstituents as chemotherapeutics and their synergistic impacts on the management of cancer.The possible modes of anticancer actions of Body Revival are multifactorial.It stimulates the immune system, protects DNA from injury, restores damaged DNA, lowers oxidative impairment, antiproliferation, cancer cell cycle arrest, initiation of apoptosis, suppression of angiogenesis and metastasis, chemo preventive or restore/protects normal cells from harmful effects of radiation.Furthermore, it is devoid of any toxic effect.The goal-oriented programmed clinical approaches are desirable to strengthen its anticancer efficacies as a safe chemotherapeutic agent.

Background and purpose Carnitine palmitoyltransferase I (CPT1), an integral outer mitochondrial protein and prime decider of fatty acid β-oxidation (FAO) has been considered to be a key therapeutic target against triple negative breast cancer (TNBC) progression and survival. Herein, we have introduced a biotin-functionalized copolymer, (Py-P(PDSMA-co-PEGMA)-b-P(Bt-PEGMA)), CP4 which can actively target CPT1 and block FAO in metastatic TNBC. Experimental Approach CP4 were synthesized using reversible addition fragmentation chain transfer or RAFT polymerization. In silico computation modelling predicted the active binding of CP4 with CPT1. Cell-based Seahorse energy efflux assay investigated the mitochondrial respiration, glycolytic function and overall ATP production rate. FACS analysis checked the mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) and cell apoptosis. Real-time quantitative reverse transcription PCR (qRT-PCR) analysed FAO-related protein expression profiles. Antitumor activities were confirmed in female breast cancer (BALB/c) mice model. Key results Negative docking score and Ramachandran plot analyses affirmed the active targeting of CP4 to CPT1. Beside, CP4 has remarkably switched the ΔΨm and produced excessive ROS followed by the reduction in glycolytic function, mitochondrial oxidative phosphorylation, FAO and thereby limited excessive ATP production. In turn, it induced metastatic growth inhibition and apoptotic cell death in TNBC cells. Importantly, CP4 has significantly improved the altered lipid and oxidative stress profiles following excellent tumor regression, and thereby advocated plausible FAO-targeted anticancer therapies. Conclusion and Implications CP4 has the potentiality of being a new age FAO-targeted anticancer therapeutics that may open up a new treatment strategy against breast cancer soon.

Recent evidence confirmed that the maximum energy in metastatic breast cancer progression is supplied by fatty acid oxidation (FAO) governed by a rate-limiting enzyme, carnitine palmitoyltransferase 1 (CPT1). Therefore, the active limitation of FAO could be an emerging aspect to inhibit breast cancer progression. Herein, for the first time, we have introduced quercetin (QT) from a non-dietary source (Mikania micrantha Kunth) to limit the FAO in triple-negative breast cancer cells (TNBC) through an active targeting of CPT1. Molecular quantification of QT was confirmed through high-performance thin-layer chromatography (HPTLC). Computational docking analyses predicted the binding affinity of QT to CPT1. Cell-based seahorse energy efflux investigated the mitochondrial respiration rate, glycolytic function and ATP production rate. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) investigated the FAO-associated gene expression. Matrigel cell invasion and fluorescence-activated cell sorting analyses investigated anti-metastatic and apoptotic cell death induction activities, respectively. In vivo antitumor activities were checked using the female breast cancer mice (BALB/c) model. QT resulted in a significant reduction in the intracellular mitochondrial respiration and glycolytic function, limiting extensive ATP production. In turn, QT elevated the reactive oxygen species (ROS) and depleted antioxidant levels to induce anti-metastatic and cell apoptosis activities. qRT-PCR resulted in active healing of altered FAO-associated gene expression which was well predicted through the successful in silico molecular binding potentiality of QT to CPT1. Subsequently, QT has shown excellent in vivo antitumor activities through the altered lipid profile and oxidative stress-healing capabilities. All the obtained data significantly grounded the fact that QT could be a promising metabolism-targeted breast cancer therapeutic.

Capparis decidua belongs to family Capparidaceae in wastelands of India. The study aim was to determine the role of C. decidua fruits on the free fatty acids (FFA) profile in fat-rich diet (FRD) dyslipidemic rats. The methanolic extract of edible fruit of C. decidua (CD) was given orally to obese dyslipidemic rats at the dose of 125 mg/kg and 250 mg/kg for consecutive 28 days. CD treatment in FRD rats significantly restricts the body weight gains. Blood lipid profile was altered dose dependently and significantly after 4-week treatment with CD to FRD. rats. It significantly (p<0.05) enhanced serum FFA especially, -linolinate, -linolinate, arachidonate, ecosapentaenoate, docosapentaenoate and docosahexaenoate. Moreover, 3-PUFA content was also enhanced (50.3% and 78.8%) in the serum of CD treated animals, whereas MUFA was lowered (31.1% and 40%). Therefore, Capparis decidua fruit has a promising role on dyslipidemia and obesity and has the capabilities to regulate beneficial free fatty acids.

Immumomodulatory actions of natural ingredients have been recognized from the time of early civilization. Though herbal medicines are equally used to treat deadly diseases, but till date there are lacks of evidences. In the present work, an herbal preparation IMT-03 was used to find out its immunostimulatory efficacy against chemotherapeutics. Although, most of the individual ingredients present in IMT-03 have been reported for their protective roles against chemotherapeutics, but there is no report in combination. Cyclophosphamide (300 mg/kg, intraperitoneally) induces immunosuppression through myelosuppression. Pretreatment with of IMT-03 at dose of 100 mg/kg and 200 mg/kg in Cyclophosphamide induced immunosuppressive mice showed dose dependently and significantly (p<0.001) improvement in total WBC and absolute neutrophil counts. It also protects the general health of animals from chemotherapeutic induced serious adverse events like signs of sickness, lethargy, immobility, reducing food habit, infections in nostrils and pinna etc. Moreover, IMT-03 has the abilities to counter the macrophages surge during the LPS challenge. The test drug also showed safe up to the oral dose of 2 g/kg. In vitro studies revealed IMT-03 has polyphenols and also radical scavenging actions. There are several evidences that polyphenols can able to modulate cytokines and chemokines signaling pathways in immune cells. Therefore, it is assumed that polyphenols present in IMT-03 either modulate the inflammatory signaling pathways or protect from oxidative stress related DNA damage in myeloid tissues.

The health benefit of coffee consumption mainly depends on chlorogenic acid (CGA), one of its major active phenolic constituent. CGA have several biological properties like anticancer, antihypertensive, hepatoprotective, neuroprotective, renoprotective, antimicrobial etc. It is assumed that different forms of coffee contains different amount of CGA. In this regards, we developed and validated a simple and cost effective chromatographic technique to identify and quantify CGA in green coffee, roasted coffee and branded instant coffee available in Indian market.